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  • Induction of Rosette-to-Lum...
    Langkabel, Jan; Horne, Arik; Bonaguro, Lorenzo; Holsten, Lisa; Hesse, Tatiana; Knaus, Alexej; Riedel, Yannick; Becker, Matthias; Händler, Kristian; Elmzzahi, Tarek; Bassler, Kevin; Reusch, Nico; Yeghiazarian, Leon Harootoonovtch; Pecht, Tal; Saglam, Adem; Ulas, Thomas; Aschenbrenner, Anna C; Kaiser, Franziska; Kubaczka, Caroline; Schultze, Joachim L; Schorle, Hubert

    Nature communications, 12/2021, Letnik: 12, Številka: 1
    Journal Article

    Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5-E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.